Recruitment of HIV/AIDS treatment-naïve patients to clinical trials in the highly active antiretroviral therapy era: influence of gender, sexual orientation and race.

BACKGROUND: In the USA, women, racial/ethnic minorities and persons who acquire HIV infection through heterosexual intercourse represent an increasing proportion of HIV-infected persons, and yet are frequently underrepresented in clinical trials. We assessed the demographic predictors of trial participation in antiretroviral-naïve patients. METHODS: Patients were characterized as trial participants if highly active antiretroviral therapy (HAART) was initiated within a clinical trial. Prevalence ratios (PRs) were obtained using binomial regression. RESULTS: Between 1996 and 2006, 30% of 738 treatment-naïve patients initiated HAART in a clinical trial. Trial participation rates for men who have sex with men (MSM), heterosexual men, and women were respectively 36.5, 29.6 and 24.3%. After adjustment for other factors, heterosexual men appeared less likely to participate in trials compared with MSM [PR 0.79, 95% confidence interval (CI) 0.57, 1.11], while women were as likely to participate as MSM (PR 0.97, 95% CI 0.68, 1.39). The participation rate in Black patients (25.9%) was lower compared with non-Black patients (37.5%) (adjusted PR 0.80, 95% CI 0.60, 1.06). CONCLUSIONS: In our clinical setting, gender did not appear to impact participation in HIV treatment trials, but Black patients were slightly less likely to participate in these trials. Considering the substantial proportion of HIV-infected patients who are Black, future trials need to consider strategies to incorporate such underrepresented populations.

Spatial analysis and mapping of sexually transmitted diseases to optimise intervention and prevention strategies.

OBJECTIVE: We analysed and mapped the distribution of four reportable sexually transmitted diseases, chlamydial infection/non-gonococcal urethritis (chlamydial infection), gonorrhoea, primary and secondary syphilis (syphilis), and HIV infection, for Wake County, North Carolina, to optimise an intervention. METHODS: We used STD surveillance data reported to Wake County, for the year 2000 to analyse and map STD rates. STD rates were mathematically represented as a spatial random field. We analysed spatial variability by calculating and modelling covariance functions of random field theory. Covariances are useful in assessing spatial patterns of disease locally and at a distance. We combined observed STD rates and appropriate covariance models using a geostatistical method called kriging, to predict STD rates and associated prediction errors for a grid covering Wake County. Final disease estimates were interpolated using a spline with tension and mapped to generate a continuous surface of infection. RESULTS: Lower incidence STDs exhibited larger spatial variability and smaller neighbourhoods of influence than higher incidence STDs. Each reported STD had a clustered spatial distribution with one primary core area of infection. Core areas overlapped for all four STDs. CONCLUSIONS: Spatial heterogeneity within STD suggests that STD specific prevention strategies should not be targeted uniformly across Wake County, but rather to core areas. Overlap of core areas among STDs suggests that intervention and prevention strategies can be combined to target multiple STDs effectively. Geostatistical techniques are objective, population level approaches to spatial analysis and mapping that can be used to visualise disease patterns and identify emerging outbreaks.

Selection for expression of the gonococcal hemoglobin receptor during menses.

All gonococci encode a hemoglobin (Hgb) receptor, but it is phase variable, and most laboratory and clinical isolates are in the Hgb receptor "off" phase. In the present study, we address the question of whether there is a selective advantage to expressing the Hgb receptor during early phases of the menstrual cycle, when Hgb is readily available from menstrual blood. Inclinical isolates collected from women, Hgb use in vitro (Hgb receptor "on" phase) was associated with a shorter time since the onset of the last menstrual cycle, (P=.031, Wilcoxon rank-sum test). Thus, there may be a selective advantage to expression of the gonococcal Hgb receptor during infection of women in the early phases of their menstrual cycles.

Clinical utility of measuring white blood cells on vaginal wet mount and endocervical gram stain for the prediction of chlamydial and gonococcal infections.

BACKGROUND: White blood cells on endocervical Gram stain and vaginal wet mount are frequently used to predict chlamydial and gonococcal infections. Previous studies provide conflicting evidence for the clinical utility of these tests. GOAL: To evaluate the clinical utility of measuring white blood cells on vaginal wet mount and endocervical Gram stain for the prediction of chlamydial infection and gonorrhea. STUDY DESIGN: Women undergoing pelvic examinations at 10 county health department family planning and sexually transmitted disease clinics were tested for chlamydial infection by ligase chain reaction assay (n = 4550) and for gonorrhea by culture (n = 4402). Vaginal wet mount and endocervical Gram stains were performed in county laboratories at the time of examination. RESULTS: The prevalences of chlamydial infection and gonorrhea were 8.8% and 3.2%, respectively. For detection of chlamydial or gonococcal infection, the likelihood ratio was 2.85 (95% CI, 2.10-3.87) for > 30 white blood cells on vaginal wet mount and 2.91 (95% CI, 2.07-4.09) for > 30 white blood cells on endocervical Gram stain. Similar results were seen for individual diagnoses either of chlamydial infection or of gonorrhea. CONCLUSION: Vaginal wet mount and endocervical Gram stain white blood cells are useful for the presumptive diagnosis of chlamydial infection or gonorrhea only in settings with a relatively high prevalence of infection or when other predictors can increase the likelihood of infection.

Relative overhydration of fat-free mass in postobese versus never-obese subjects.

Obese subjects who undergo gastrointestinal surgery for weight reduction have relatively greater loss of body cell mass (BCM) than of extracellular fluid. Although the mechanism is uncertain, an implication is that weight-reduced, surgically treated obese subjects are relatively overhydrated. The present investigation explored whether diet-treated postobese (PO) subjects also are relatively overhydrated. Ten PO participants were recruited over a two-year period and matched to never-obese (NO) people by age (+/- 4 years), weight (+/- 3 kg), height (+/- 5 cm), race, and gender. PO participants had lost > or = 18.5 kg and had maintained this loss for 2-16 years. Body density (Db), total body water (TBW), and bone mineral content (BMC) were measured by hydrodensitometry, tritium dilution, and dual-energy X-ray absorptiometry, respectively. Fat and fat-free mass (FFM) were derived using a four-compartment model. BCM was calculated from total body potassium (TBK) measured with a whole body counter. The results indicate that PO subjects were relatively overhydrated and had reduced BCM compared to NO subjects (p < 0.05). These observations are important for interpreting body weight, body composition, and metabolic data of obese subjects who lost weight and maintained their weight loss over the long term.

Selective screening for chlamydial infection: which criteria to use?

BACKGROUND: Screening sexually active women for Chlamydia trachomatis is necessary to detect asymptomatic infections. Selective screening is a common strategy because universal screening is too costly in many settings. In order to guide local programs in the choice of selective screening criteria, we examined the performance of previously proposed screening criteria for C. trachomatis. METHODS: A clinic-based, cross-sectional study was conducted in public family planning and sexually transmitted disease (STD) clinics in ten counties in North Carolina. Women (n = 4471 in family planning and n = 2201 in STD clinics) undergoing pelvic examination were enrolled consecutively. Nine sets of screening criteria, including age alone, were compared using sensitivity, specificity, number of tests required and receiver-operator characteristic (ROC) analysis. All women underwent testing with ligase chain reaction assay of cervical specimens to identify C trachomatis infection. RESULTS: The prevalence of C. trachomatis was 7.8% and 11.0% in family planning and STD clinics, respectively. The sensitivities of published criteria ranged from 0.50 to 0.97. Specificities ranged from 0.05 to 0.66. In family planning clinics, the best performing criteria would detect 84% of infections while screening 51% of women. In STD clinics, the same criteria would detect 83% of infections but require testing 67% of women. Testing women aged < or =22 would detect 77% of infections in family planning and 74% of infections in STD clinics, while testing 51% and 48% of the women, respectively. CONCLUSIONS: When site-specific criteria cannot be developed, age alone is an acceptable strategy for selective screening for chlamydial infection.

Self-reported sexual activity and condom use among symptomatic clients attending STD clinics.

BACKGROUND AND OBJECTIVES: A cross-sectional survey of sexually transmitted disease (STD) patients assessed sexual activity and condom use during the time between STD symptom onset and clinic attendance. STUDY DESIGN: Patients were asked to report sexual activity and condom use while STD symptoms were present. Medical records were abstracted for diagnoses. RESULTS: The study population (n = 3025) was predominately African American (75.3%) and male (63.5%), with a mean age of 28.1 years. Sexual activity while experiencing STD symptoms was reported by 39.7% of 2,508 symptomatic patients, 17.2% of whom reported always using a condom. Logistic regression models identified the significant independent determinants of sexual intercourse while symptomatic were duration of symptoms before clinic visit [0-7 days versus 8 or more days, OR = 5.9]; race [African American versus other races (primarily Hispanics), OR = 2.1]; and gender [men versus women, OR = 1.5]. Older age [> or = 30 years versus 18-29 years, OR = 1.5] and higher education attainment [> or = high school versus > high school, OR = 1.5] were the significant factors associated with reporting always using a condom. CONCLUSION: These data suggest patient groups with behaviors likely to enhance STD transmission could be targeted for educational messages.

PIP: Patients seen at 10 public health sexually transmitted disease (STD) clinics in Baltimore, MD; Birmingham, AL; Chicago, IL; Durham, NC; New Orleans, LA; Raleigh, NC; and San Diego, CA, from August 1993 through June 1994 were asked to participate in a cross-sectional survey assessing sexual activity and condom use during the time between STD symptom onset and clinic attendance. Patients were asked to report sexual activity and condom use while STD symptoms were present. The sample of 3025 study participants was 75.3% African-American and 63.5% male, aged 18-73 years, of mean age 28.1 years. Sexual activity while experiencing STD symptoms was reported by 39.7% of 2508 symptomatic patients, of whom 17.2% reported always using a condom. Multivariate logistic regression found that factors associated with sexual activity while symptomatic include duration of symptoms for 7 or fewer days, being Black, and being male. In addition, such regression found that symptomatic patients who always used condoms were more likely to be aged 30 years or older, and to have at least a high school education.

Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1, from the flowers of Eucalyptus albens.

Sideroxylonal C (3), a new phloroglucinol dimer, was isolated from the flowers of Eucalyptus albens through bioassay-guided fractionation. The structure elucidation was based on 1D and 2D NMR experiments, MS analysis, and comparison with sideroxylonals A (1) and B (2). Sideroxylonal C inhibited human plasminogen activator inhibitor type-1 at 4.7 microM without any significant effect on human tissue plasminogen activator.

Self-treatment patterns among clients attending sexually transmitted disease clinics and the effects of self-treatment on STD symptom duration. The Study Group.

OBJECTIVE: To assess patterns of self-treatment and its effects on the duration of sexually transmitted disease (STD) symptoms before medical care. METHODS: A cross-sectional interview survey in public STD clinics (7 U.S. cities). Patients, seeking treatment for STD symptoms or having a known infected sexual contact, reported self-treatment behaviors and symptom duration. Additional data were abstracted from medical charts. RESULTS: Self-treatment, primarily over-the-counter topical medications (54.8%), was reported by 21.8% of 2,508 symptomatic patients. Self-treaters were significantly more likely to be African-American (odds ratio [OR] = 1.8), female (OR = 1.7), over age 30 (OR = 1.3), report > 1 symptom (OR = 1.4), and report a genital lesion (OR = 2.1). Symptom duration was 2 days longer among self-treaters (p < 0.01). African-Americans (OR = 1.5), men (OR = 1.2), and self-treaters of symptoms other than genital lesions (OR = 1.4) had a significantly longer time from symptom onset to receiving medical care. CONCLUSIONS: Self-treatment is common among patients with STDs. Self-treatment of a genital lesion, unlike certain demographic factors and self-treatment of other STD symptoms, did not prolong the time to medical treatment.

Characterisation of Neisseria gonorrhoeae in semen during urethral infection in men.

OBJECTIVE: To determine the number of Neisseria gonorrhoeae organisms in urine and semen in men with gonococcal urethritis, and to compare selected phenotypic characteristics of organisms harvested from the urethra and semen. DESIGN: Samples from two groups of subjects were examined. Patients with symptomatic urethritis receiving treatment at an STD clinic, as well as six subjects with experimental urethritis. Semen and urine specimens were obtained after the urethral exudate was sampled. RESULTS: Using quantitative cultures, we found an average of 6 x 10(6) gonococci in urine or semen of 17 men with symptomatic urethritis seeking treatment at an STD clinic, and 2 x 10(4) gonococci in secretions of six male subjects with early experimental infection. Gonococcal outer membrane opacity (Opa) proteins and lipo-oligosaccharide (LOS) recovered from urine and semen of these subjects were very similar. CONCLUSIONS: Men with symptomatic gonorrhoea excrete a large number of gonococci in semen which is not affected by the duration of symptoms. The similar phenotype of organisms in urine and semen suggests the bacteria come from the same compartment. These data help to explain the efficiency of gonococcal transmission from men to their partners, and identify an appropriate target for a preventative vaccine or immunotherapy designed to reduce the inoculum in infected patients.

Time required for elimination of Neisseria gonorrhoeae from the urogenital tract in men with symptomatic urethritis: comparison of oral and intramuscular single-dose therapy.

BACKGROUND AND OBJECTIVES: The spread of sexually transmitted diseases (STDs), including gonorrhea, is affected by the duration of infection. Oral antibiotic therapy for gonococcal infection has been shown to be as effective as conventional intramuscular injection with ceftriaxone. Rapid cure would be expected to limit further spread of gonorrhea. However, the speed with which Neisseria gonorrhoeae is eliminated from the urogenital tract has not been evaluated. GOAL OF THIS STUDY: To determine the time required for elimination of Neisseria gonorrhoeae for the urine, mucosa, and semen in male subjects after treatment with ceftriaxone (250 mg intramuscularly), ciprofloxacin (500 mg by mouth, single dose) or cefixime (400 mg by mouth, single dose.) RESULTS: In 14 subjects, gonococci were eliminated from the urine within 4 hours of therapy and the mucosa within 24 hours after therapy. In 9 additional subjects, gonococci were eliminated from the semen by 24 hours after therapy. CONCLUSIONS: These results support the efficacy of single-dose oral therapy for gonorrhea and suggest that earlier follow-up for proof of cure in clinical trials of new antibiotics for gonorrhea may be acceptable. Rapid elimination of gonorrhea reduces the risk for continued transmission of the organism.

Prospective, randomized comparison of sequential intravenous followed by oral ciprofloxacin with intravenous ceftazidime in the treatment of serious infections.

In a prospective, comparative trial, 47 hospitalized patients with serious infections that required parenteral antibiotic therapy were randomly assigned to receive either ciprofloxacin (200 mg every 12 hours intravenously followed by 500 mg every 12 hours orally at a time dependent on the patients' clinical and bacteriologic responses) or ceftazidime (2 g every eight to 12 hours intravenously). All evaluable subjects (39 patients) had documented infections, 23 percent of which were associated with bacteremia. The mean/median duration of intravenous antibiotic use for ciprofloxacin was 7.37/five days and for ceftazidime 9.95/seven days; 63 percent of the ciprofloxacin patients received an additional 17 days of oral therapy with ciprofloxacin, whereas intravenous therapy with ceftazidime was followed by an average of 12 days of an oral regimen in 55 percent of patients. Overall response rates for patients receiving ciprofloxacin and ceftazidime were 76 percent (16 of 21) and 82 percent (18 of 22), respectively. Four out of five bacteremias in each group were successfully treated. Overall, 69 percent of the pathogens were gram-negative aerobes, and 47 percent of the infections involved the urinary tract. Failure of therapy was most often associated with pneumonia (two of five failures with ciprofloxacin and three of four failures with ceftazidime). Adverse effects occurred in approximately 20 percent of patients in each group and were mild and reversible. Superinfections occurred in five of 19 (26 percent) ciprofloxacin recipients and seven of 20 (35 percent) ceftazidime recipients. All fungal superinfections involved the genitourinary tract and occurred most often in association with chronic indwelling catheters. Enterococcal superinfections occurred in both groups (a bacteremic urinary tract infection in a ceftazidime patient and osteomyelitis in a ciprofloxacin patient). Clostridium difficile-associated diarrhea was documented in a ceftazidime recipient. The mean duration of hospitalization following the onset of antibiotic treatment was 10.45 days in the ciprofloxacin group and 12.95 days in the ceftazidime group. Sequential intravenous/oral ciprofloxacin was as safe and effective as intravenous ceftazidime in the treatment of infections due to susceptible gram-positive and gram-negative organisms.

Coregulation of NADPH oxidase activation and phosphorylation of a 48-kD protein(s) by a cytosolic factor defective in autosomal recessive chronic granulomatous disease.

The mechanisms regulating activation of the respiratory burst enzyme, NADPH oxidase, of human neutrophils (PMN) are not yet understood, but protein phosphorylation may play a role. We have utilized a defect in a cytosolic factor required for NADPH oxidase activation observed in two patients with the autosomal recessive form of chronic granulomatous disease (CGD) to examine the role of protein phosphorylation in activation of NADPH oxidase in a cell-free system. NADPH oxidase could be activated by SDS in reconstitution mixtures of cytosolic and membrane subcellular fractions from normal PMN, and SDS also enhanced phosphorylation of at least 16 cytosolic and 14 membrane-associated proteins. However, subcellular fractions from CGD PMN plus SDS expressed little NADPH oxidase activity, and phosphorylation of a 48-kD protein(s) was selectively defective. The membrane fraction from CGD cells could be activated for NADPH oxidase when mixed with normal cytosol and phosphorylation of the 48-kD protein(s) was restored. In contrast, the membrane fraction from normal cells expressed almost no NADPH oxidase activity when mixed with CGD cytosol, and phosphorylation of the 48-kD protein(s) was again markedly decreased. Protein kinase C (PKC) activity in PMN from the two patients appeared to be normal, suggesting that a deficiency of PKC is not the cause of the defective 48-kD protein phosphorylation and that the cytosolic factor is not PKC. These results demonstrate that the cytosolic factor required for activation of NADPH oxidase also regulates phosphorylation of a specific protein, or family of proteins, at 48 kD. Although the nature of this protein(s) is still unknown, it may be related to the functional and phosphorylation defects present in CGD PMN and to the activation of NADPH oxidase in the cell-free system.